Delivering tumor treating fields (ttfields) using implantable transducer arrays

Abstract

To solve the problem in which the bulk of a system can be large.SOLUTION: Tumor treating fields (TTFields) can be delivered by implanting a plurality of sets of implantable electrode elements within a person's body. Temperature sensors positioned to measure the temperature at the electrode elements are also implanted, along with a circuit that collects temperature measurements from the temperature sensors. In some embodiments, an AC voltage generator configured to apply an AC voltage across the plurality of sets of electrode elements is also implanted within the person's body.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 811,311, filed February 17, 2019, which is incorporated herein by reference in its entirety. [Background technology]

[0002] TTFields (Tumor Treating Fields) therapy is a proven approach for treating tumors. Referring to FIG. 1 , in the prior art Optune® system for delivering TTFields, TTFields are delivered to a patient via four transducer arrays placed on the patient's skin in close proximity to the tumor. These transducer arrays are configured in two pairs. One pair (A / A) is positioned on the left and right sides of the head, and the other pair (B / B) is positioned on the front and back of the head. Each transducer array is connected to an AC voltage generator via a multi-wire cable. The AC voltage generator (a) delivers AC current through one pair of arrays during a first time period, then (b) delivers AC current through the other pair of arrays during a second time period, and then repeats steps (a) and (b) for the duration of the treatment period.

[0003] Each transducer array is constructed as a set of capacitively coupled electrode elements (approximately 2 cm in diameter) interconnected by flexible wires. Each electrode element comprises a ceramic disc sandwiched between a layer of conductive medical gel and adhesive tape. When these arrays are placed on a patient, the medical gel adheres to the contours of the patient's skin, ensuring good electrical contact between the body and the device. The adhesive tape holds the entire array in place on the patient as they go about their daily activities.

[0004] The amplitude of the alternating current delivered through the transducer array is controlled so that the skin temperature (as measured on the skin beneath the transducer array) does not exceed a safety threshold of 41°C. Temperature measurements on the patient's skin are obtained using thermistors located under some of the disks of the transducer array. In existing Optune® systems, each array includes eight thermistors, with one thermistor positioned under each disk of the array (note that most arrays include nine or more disks, in which case temperature measurements are taken under only a subset of the disks in the array).

[0005] The thermistors in each of the four arrays are connected via long wires to an electronic device called a "cable box." Temperature measurements are taken from all 32 thermistors (four arrays x eight thermistors per array A, A, B, B) and converted to digital values ​​for each thermistor. These measurements are then sent from the cable box to the AC voltage generator via two additional wires that facilitate bidirectional digital serial communication between the cable box and the AC voltage generator. A controller in the AC voltage generator uses these temperature measurements to control the current delivered through each pair of arrays A, A, B, B to maintain a temperature below 41°C on the patient's skin. This current itself is delivered to each array via additional wires that run from the AC voltage generator through the cable box to the arrays (i.e., one wire for each array).

[0006] In the existing Optune® system, there are four long 10-wire cables (one running between each array and the cable box) and one 8-wire spiral cord running between the AC voltage generator and the cable box. Each 10-wire cable has eight wires to carry signals from the eight thermistors, one wire shared by all eight thermistors, and one wire to transmit the TTFields signal to the array. The 8-wire spiral cord has one wire to power the cable box (Vcc), one wire to ground the cable box, two wires for data communication (to transmit temperature readings to the AC voltage generator), and four wires for the TTFields signal (i.e., one for each of the four arrays). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] US Patent Application Publication No. 2018 / 0050200 [Patent Document 2] U.S. Patent No. 9,910,453 [Non-patent literature]

[0008] [Non-Patent Document 1] Dissanayake et al., “IFMBE proceeding” vol.23 Summary of the Invention [Means for solving the problem]

[0009] One aspect of the present invention relates to a first device for delivering a tumor-treating electric field. The first device comprises a plurality of electrode element sets, each of which is configured for implantation within a human body. The first device also comprises a plurality of temperature sensors configured for implantation within the human body and positioned relative to the electrode element sets to measure temperature at each of the electrode element sets. The first device also comprises a circuit configured for implantation within the human body and configured to collect temperature measurements from the plurality of temperature sensors. The first device also comprises an AC voltage generator configured for implantation within the human body and configured to apply an AC voltage across the plurality of electrode element sets.

[0010] Some embodiments of the first device further comprise an inductive coupling circuit configured to be implanted within a human body and configured to power the AC voltage generator.

[0011] Some embodiments of the first device further comprise a battery configured to be implanted within the human body and configured to power the AC voltage generator. Optionally, these embodiments may further comprise an inductive coupling circuit configured to be implanted within the human body and configured to charge the battery.

[0012] In some embodiments of the first apparatus, each of the electrode element sets comprises a plurality of capacitively coupling electrode elements. Optionally, in these embodiments, each of the capacitively coupling electrode elements comprises a ceramic disc.

[0013] In some embodiments of the first device, each of the temperature sensors comprises a thermistor. In some embodiments of the first device, the plurality of electrode element sets, the plurality of temperature sensors, the circuitry, and the AC voltage generator are all implanted within a human body.

[0014] Another aspect of the present invention relates to a second device for delivering a tumor-treating electric field, the second device comprising a plurality of electrode element sets, each of the electrode element sets configured for implantation within a human body, the second device also comprising a plurality of temperature sensors configured for implantation within the human body and positioned to measure temperature at each of the electrode element sets, and the second device also comprising circuitry configured for implantation within the human body and configured to collect temperature measurements from the plurality of temperature sensors.

[0015] In some embodiments of the second device, each of the electrode element sets comprises a plurality of capacitively coupled electrode elements. In some embodiments of the second device, each of the temperature sensors comprises a thermistor. In some embodiments of the second device, the plurality of electrode element sets, the plurality of temperature sensors, and the circuit are all implanted within the human body.

[0016] Another aspect of the present invention relates to a third device for delivering a tumor-treating electric field, the third device comprising a plurality of electrode element sets, each of the electrode element sets configured for implantation within a human body, a plurality of temperature sensors configured for implantation within the human body and positioned to measure temperature at each of the electrode element sets, and an AC voltage generator configured for implantation within the human body and configured to apply an AC voltage across the plurality of electrode element sets.

[0017] Some embodiments of the third device are configured to be implanted within a human body and further comprise an inductive coupling circuit configured to power the AC voltage generator.

[0018] Some embodiments of the third device further comprise a battery configured to be implanted within the human body and configured to power the AC voltage generator. Optionally, these embodiments may further comprise an inductive coupling circuit configured to be implanted within the human body and configured to charge the battery.

[0019] In some embodiments of the third apparatus, each of the sets of electrode elements comprises a plurality of capacitively coupling electrode elements. Optionally, in these embodiments, each of the capacitively coupling electrode elements may comprise a ceramic disc.

[0020] In some embodiments of the third apparatus, each of the temperature sensors comprises a thermistor. In some embodiments of the third apparatus, the plurality of electrode element sets, the plurality of temperature sensors, and the AC voltage generator are all implanted within the human body. [Brief explanation of the drawings]

[0021] [Figure 1] FIG. 1 is a block diagram of a prior art Optune® device used to deliver TTFields to the human head. [Figure 2] FIG. 1 is a block diagram of an embodiment that reduces the number of conductors in each cable that must pass through the patient's skin. [Figure 3] FIG. 1 is a block diagram of an embodiment in which the transducer array and hub are both implanted within the patient's body. [Figure 4] FIG. 10 illustrates an alternative approach using implantable electrodes, where the electrodes, hub, and AC voltage generator are all implanted within the patient's body. [Figure 5] FIG. 5 shows a variation of the embodiment of FIG. 4 in which power is supplied to the hub and AC voltage generator using a wireless connection. [Figure 6] FIG. 1 illustrates an embodiment using implantable electrodes powered by an implantable battery. [Figure 7] FIG. 10 illustrates an embodiment in which current to individual electrode elements can be switched on or off based on the state of a set of electrically controlled switches. [Figure 8] FIG. 8 is a schematic diagram of a circuit suitable for implementing these switches in the embodiment of FIG. 7. DETAILED DESCRIPTION OF THE INVENTION

[0022] Various embodiments will now be described in detail with reference to the accompanying drawings, in which like reference numerals represent like elements and dashed lines indicate the presence of embedded components.

[0023] Instead of using a transducer array positioned on the patient's skin to deliver TTFields (as in the embodiment of FIG. 1 above), the embodiments described herein use a transducer array that is implanted within the patient's body to deliver TTFields. Implanting a transducer array can provide a number of potential advantages. These potential advantages include: (1) concealing the array from those interacting with the patient; (2) improved patient comfort (by avoiding skin irritation, a burning sensation, and / or restricted movement that may result from the array being positioned on the patient's skin); (3) improved electrical contact between the transducer array and the patient's body; (4) eliminating the need to shave the area where the array is placed (as hair growth would interfere with the delivery of TTFields); (5) avoiding the risk of the transducer array becoming dislodged, disrupting the delivery of TTFields; and (6) significantly reducing the power required to deliver TTFields (e.g., by reducing the physical distance between the transducer array and the tumor, e.g., by preventing contact with the skull). (7) significantly reducing the weight of the device that must be carried by the patient (e.g., by taking advantage of the reduced power requirements to use smaller batteries); (8) avoiding skin irritation that can occur when a transducer array is positioned on the patient's skin; and (9) enabling TTFields to be delivered to anatomical structures that cannot be treated using a transducer array positioned on the patient's skin (e.g., the spinal cord, which is surrounded by highly conductive cerebrospinal fluid and further surrounded by the bony structures of the spinal column, both of which interfere with the penetration of TTFields into the spinal cord itself).

[0024] It should be noted that in any of the embodiments described herein, it is important to include a sensor (such as a thermistor) to measure the temperature on or near the transducer array so that the tissue temperature can be controlled and thermal damage to the tissue avoided. Where a given transducer array is comprised of multiple individual elements (e.g., ceramic discs), it is preferable to distribute multiple temperature sensors (e.g., thermistors) among these multiple individual elements.

[0025] One approach (not shown) for using implantable electrodes has a similar block diagram to the prior art embodiment of FIG. 1 described above, but differs in that the transducer arrays A, A, B, B are all implanted within the patient (e.g., between the scalp and skull or adjacent to the dura mater). This approach enjoys the advantages (1) through (8) described above, but also suffers from many disadvantages. More specifically, each transducer array is connected to a cable box / AC voltage generator via a relatively long and bulky 10-wire cable (one wire for applying AC voltage to each transducer array and nine wires used to obtain temperature readings from eight different locations on each transducer array) that extends outside the body through a surgical incision or port. The use of this 10-wire cable can result in a bulky system. Furthermore, having components passing through human skin and into the head increases the risk of infection, which can be particularly problematic in the brain.

[0026] FIG. 2 illustrates an improvement over the approach described in the previous paragraph. In this approach, the number of conductors in each cable that must pass through the patient's skin is reduced from 10 to 4, thereby significantly reducing the bulk and size of these cables. This can be achieved, for example, by implanting additional electrodes E adjacent to each of the implanted transducer arrays A and B and utilizing a hub-based architecture. When a hub-based architecture is used, each of the electronic blocks E includes a multiplexer that reduces the number of conductors required to obtain temperature measurements from 9 to 3, and a hub 30h is used to collect temperature readings from each transducer array and transfer those readings to an AC voltage generator 30g. The AC voltage generator 30g can then control the current applied to each of the transducer array pairs A / A and B / B to ensure that the transducer arrays do not overheat. Examples of circuits that may be used for implementation of these electronic blocks E and hubs can be found in U.S. Patent Application Publication No. 2009 / 0129999, entitled "Temperature Measurement in Arrays for Delivering TTFields," which is incorporated herein by reference in its entirety. While this embodiment reduces the size and bulk of the wires that must pass through human skin, providing the benefits (1)-(8) discussed above, it does not mitigate the infection risks associated with components passing through human skin and into the head.

[0027] FIG. 3 illustrates a variation on the approach of FIG. 2. In the embodiment of FIG. 3, instead of positioning the hub outside the patient's body and extending four cables through the patient's skin (as in FIG. 2), the electronics E, transducer arrays A and B, and hub 30h are implanted inside the patient's body. In the embodiment of FIG. 3, only one cable (i.e., the cable extending between hub 30h and AC voltage generator 30g) must pass through the patient's skin. Optionally, this cable is connectorized using port 12 as shown. In the example shown in FIG. 3, hub 30h is positioned somewhere within the patient's thorax, and four four-conductor cables extend between electronics E and transducer arrays A and B within the patient's head, with hub 30h located within the patient's thorax. This positioning is advantageous because no wires are routed directly from the outside world into the patient's head, thus reducing the risk of serious infection. However, in a variation of the embodiment of FIG. 3, hub 30h may be positioned within the patient's head, in which case port 12 providing access would also be positioned in the patient's head.

[0028] In the embodiment of Figure 3, hub 30h collects temperature measurements from each of transducer arrays A, B via electronics E and forwards these temperature measurements to AC voltage generator 30g via port 12. AC voltage generator 30g can then control the current applied to each of transducer array pairs A / A and B / B to ensure that the transducer arrays do not overheat. This embodiment also provides advantages 1-8 described above.

[0029] FIG. 4 shows another approach that uses implantable electrodes and provides advantages 1-8 described above. In this embodiment, electrodes A and B, a hub 30h, and an AC voltage generator 30g are all implanted within the patient. Power for the hub 30h and the AC voltage generator 30g is supplied through a port 14 positioned somewhere on the patient's skin (e.g., the thorax). The power source (e.g., a battery) in this embodiment is external, and the battery provides power to the hub 30h and the AC voltage generator 30g through the port. The port 14 is connected to the hub 30h and the AC voltage generator 30g via appropriate wiring (e.g., a two-conductor cable).

[0030] Because effective delivery of TTFields requires power delivery on the order of 10 W to 100 W, care must be taken to minimize heat dissipation in all embodiments in which the AC voltage generator 30g is implanted within the patient (including this embodiment of FIG. 4 ), since any inefficiency can result in heating of the tissue surrounding the field generator, thereby resulting in thermal damage to the patient's internal tissue. To accomplish this, the AC voltage generator 30g must operate with very high efficiency. An example of a circuit suitable for implanting a high-efficiency AC voltage generator is described in U.S. Patent Application Publication No. 2007 / 0122944, entitled “High Voltage, High Efficiency Sine Wave Generator with Pre-Set Frequency and Adjustable Amplitude,” which is incorporated herein by reference in its entirety.

[0031] Optionally, the AC voltage generator 30g in these embodiments may operate by starting from a low-voltage AC signal and amplifying and filtering the signal using a circuit incorporating a transformer and an LC filter. In some embodiments, a separate circuit incorporating a transformer and an LC filter may be connected to each transducer array (or even to each element of each transducer array). In these embodiments, the low-voltage signal generator may be connected to each array (or element) via wires located remotely from the array. In this configuration, heat generated by losses in the system is spread over a larger volume, reducing the risk of thermal damage to tissue and allowing for the delivery of higher electric field strengths. To further reduce losses, the circuitry on each array (or element) can be designed with switches to switch the incoming low-voltage signal from the signal generator, potentially reducing losses in the system associated with switching in the array.

[0032] Optionally, the power source in the embodiment of Figure 4 may comprise multiple small batteries woven into the fabric strip. This type of design allows for the delivery of higher power for longer periods of time while minimizing discomfort to the patient.

[0033] FIG. 5 illustrates a variation on the embodiment of FIG. 4 that also provides advantages 1-8 described above. In the embodiment of FIG. 5, instead of providing power directly to the hub 30h and AC voltage generator 30g via a wired connection that passes from the outside world into the patient's body via a port 14 placed on the person's skin (as in FIG. 4), in the embodiment of FIG. 5, power is provided to the hub 30h and AC voltage generator 30g using a wireless connection. This may be achieved, for example, by implanting a first circuit 21 inside the patient's body near the patient's skin. The first circuit is configured to receive energy via inductive coupling. A second circuit 22 (which may optionally be battery and / or AC mains powered) is configured to transmit energy to the first circuit 21 via inductive coupling. The second circuit 22 is positioned adjacent to the first circuit 21 outside the patient's body during operation, so that energy can be inductively coupled from the second circuit 22 into the first circuit 21. The configuration of these circuits 21, 22 for transmitting and receiving energy by inductive coupling is well known in the art and is commonly used for charging mobile phones and the like, for example.

[0034] Optionally, the bulk and weight of the hardware that must be carried by the patient can be advantageously reduced by providing multiple copies of the second circuit 22 in various locations frequently visited by the patient. For example, one copy of the second circuit 22 may be provided in the patient's office, a second copy of the second circuit 22 in the patient's car, a third copy of the second circuit 22 in the patient's living room, and a fourth copy of the second circuit 22 in or near the patient's bed. When multiple copies of the second circuit 22 are provided, the patient positions the implanted first circuit 21 adjacent to an inductive coupling region near one of the second circuits 22, such that the nearby second circuit 22 can inductively couple to power the implanted AC voltage generator 30g. This configuration can be particularly advantageous for people who travel to various locations in a repetitive pattern (e.g., people who drive the same car to work every day, work at the same desk every day, rest in the same living room every night, and sleep in the same bed every night). Optionally, multiple copies of the second circuit 22 may be incorporated into the mattress, allowing the patient to move around on the mattress without having to be hardwired while sleeping.

[0035] FIG. 6 illustrates yet another embodiment that uses implanted electrodes and provides advantages (1) through (8) described above. Notably, the battery 25 in the embodiment of FIG. 6 is implanted within the patient's body, and the implanted battery 25 is charged inductively. One drawback to this design is that the implanted battery 25 must store a relatively large amount of energy. Therefore, inductive charging of the battery 25 requires the generation of a large magnetic flux over a long period of time. One approach to overcoming this problem is a system in which a mattress incorporating a coil is used. The patient sleeps on the mattress, and the battery 25, which powers the TTFields device, is charged while the patient sleeps. In other embodiments, the coil may surround the bed.

[0036] Alternatively, a transcutaneous energy transmission system (see, for example, Non-Patent Document 1) may be used to charge the implanted battery 25. In this case, a coil connected to a circuit designed to charge the implanted battery is implanted percutaneously. Charging is performed by the patient using a separate device 24 placed near the implanted coil 23. This external device may be secured to the patient's body using clothing designed to fit snugly against the body or using a medical adhesive. The patient only needs to use the external charger to charge the implanted battery. This may be done overnight, for example, while the patient is asleep, thereby minimizing the need for the patient to carry an external device.

[0037] Optionally, implanted transducer array elements can be configured to allow dynamic modification of the electric field distribution to optimize TTFields delivery. Unlike with external transducer arrays, once implanted, these transducer arrays make it impractical to adjust the transducer array's position to optimize the electric field distribution within the patient. Therefore, when implantable arrays are used, an alternative approach to controlling the electric field distribution within the patient is desirable. One suitable approach for this purpose is to implant a transducer array with a relatively large number of switchable elements. In this case, the electric field can be shaped by selecting a subset of the array elements that are switched on when the electric field is delivered. As the tumor changes over time (response or progression), the electric field distribution can be altered by changing the array elements that generate the electric field.

[0038] Optionally, in any of the above-described embodiments, the transducer array may be positioned on the dura mater. An advantage of this configuration is that the electric field does not need to pass through the highly resistive layer of the skull, thereby reducing the power required to deliver TTFields to the brain. At the same time, this placement reduces the need for invasive placement of these arrays within the brain, reducing the risk of damage to brain tissue and, potentially, infection. This configuration also allows for the delivery of TTFields to a large portion of the brain, as opposed to delivering TTFields only to the tumor. In some cases, treating a large portion of the brain may be advantageous, for example, when treating the brain for metastases. In some embodiments, when treating body regions other than the head, subcutaneous placement of the array may allow for treatment of a large area. In other embodiments, the array may be placed near the tumor. Placement near the tumor allows for localized delivery of TTFields and reduces the power required to deliver the electric field.

[0039] In any of the above embodiments, any component described as being implanted must be configured to be implanted prior to actual implantation within the human body, meaning that the component must be sized to fit within the implant location and any surfaces that will come into contact with tissue within the human body must be biocompatible.

[0040] Optionally, in any of the above embodiments, when the transducer arrays are implanted in close proximity to a tumor, the arrays can be made from or coated with a cytotoxic drug (e.g., platinum). The electric field induced electrolysis is expected to result in the release of platinum into the area surrounding the tumor. Platinum is known to be cytotoxic to cancer cells, and thus, platinum release into the tumor may advantageously enhance the anti-cancer effects of TTFields treatment.

[0041] Optionally, in any of the above-described embodiments, the transducer arrays A, B and electronics E implanted within the human head may be designed as described below in connection with Figure 7. An advantage of this configuration is that the average electric field strength may be maximized and the risk of heating may be minimized by individually monitoring and adjusting the current to each electrode element in each transducer array, thereby improving the efficiency of TTFields delivery. These embodiments operate by alternately switching the current on and off to individual electrode elements, so that individual electrode elements begin to heat up in a way that reduces the average current through the electrode elements without affecting the current through the remaining electrode elements (which do not overheat).

[0042] For example, assume that a 500 mA current is passing through a transducer array with 10 electrode elements, and that only one of the electrode elements begins to overheat. Further, assume that to prevent overheating of the single electrode element, it becomes necessary to reduce the current passing through this single electrode element by 10%. The embodiments described herein allow for a 10% reduction in the average current passing through this single electrode element by switching the current through this single electrode element on and off at a 90% duty cycle while leaving current on full time for all remaining electrode elements. Note that the switching speed must be fast enough so that the instantaneous temperature of this single electrode element is not excessively high given the thermal inertia of the electrode element. For example, a 90% duty cycle can be achieved by switching the current on for 90 ms and off for 10 ms. In some preferred embodiments, the current on / off switching period is less than 1 s.

[0043] When this approach is utilized, the current through the remaining nine electrode elements can be left unchanged (i.e., 50 mA per electrode element), and only the current through this single electrode element is reduced to an average of 45 mA. In this case, the net total current average through the transducer array will be 495 mA (i.e., 9 x 50 + 45), which means that significantly more current can be coupled into the body without any of the electrode elements overheating.

[0044] Furthermore, the system can be configured to increase the current through the remaining nine electrode elements to compensate for the drop in current through this single electrode element. For example, the current through the remaining nine electrode elements can be increased to 50.5 mA per electrode element (e.g., by sending a request to the AC voltage generator to increase the voltage by 1%). When this solution is implemented, the average net total current through the entire transducer array will be (9 electrodes x 50.5 mA + 1 electrode x 50.5 mA x 0.9 duty cycle) = 499.95 mA, which is very close to the original 500 mA current.

[0045] If at some later point (or even simultaneously) the temperature of the second electrode element begins to overheat, a similar technique (i.e., reducing the duty cycle from 100% to any percentage less than 100%) can be utilized to prevent overheating of the second electrode element.

[0046] In some embodiments, this technique can be utilized to individually customize the duty cycle at each electrode element to maximize the current through each electrode element without overheating. Optionally, instead of taking corrective action to reduce the duty cycle only if a given electrode element begins to overheat, the system may be configured to individually pre-set the duty cycle at each electrode element in a given transducer array to balance the temperature among all electrode elements in the array. For example, the system may be configured to individually set the duty cycle at each electrode element to maintain a temperature that remains near the set temperature of each electrode element. Optionally, the system may be configured to send requests to the AC voltage generator to increase or decrease the voltage as necessary to achieve this result.

[0047] This approach can be utilized to ensure that any electrode element carries the maximum possible average current (without overheating), thereby increasing the electric field strength at the tumor and resulting in corresponding improved treatment.

[0048] FIG. 7 illustrates one embodiment in which current is periodically switched on and off for individual electrode elements that begin to overheat. Hub / AC voltage generator 30 has two outputs (OUT1 and OUT2), each with two terminals. Hub / AC voltage generator 30 generates an AC signal (e.g., a 200 kHz sine wave) between the two terminals of each output in an alternating sequence (e.g., activating OUT1 for one second and then activating OUT2 for one second in an alternating sequence). A pair of conductors 51 connects to the two output terminals of OUT1, each of which leads to a respective one of left and right transducer assemblies 31, 32. Each of these transducer assemblies includes a plurality of electrode elements 52 (which collectively correspond to transducer arrays A, B in FIGS. 2-6) and electronic components 56, 85 (which correspond to electronics E in FIGS. 2-6). A second pair of conductors 51 are connected to the two terminals of OUT2, each of which continues to a respective one of the front and rear transducer assemblies (not shown), the structure and operation of which are similar to the structure of the left and right transducer assemblies 31, 32 shown in Figure 7.

[0049] Each transducer assembly 31, 32 includes a plurality of electrode elements 52. In some preferred embodiments, each of these electrode elements 52 is a capacitively coupled electrode element. However, in the embodiment of FIG. 7, rather than wiring all of these electrode elements 52 in parallel, an electrically controlled switch (S) 56 is wired in series with each electrode element (E) 52, and all of these S+E combinations 56+52 are wired in parallel. Each switch 56 is configured to switch on / off independently of the other switches based on the state of a respective control input received from a digital output of each controller 85. When a given one of these switches 56 is on (in response to a first state of the respective control input), current can flow between the conductor 51 and each electrode element 52. Conversely, when a given one of these switches 56 is off (in response to a second state of the respective control input), current cannot flow between the conductor 51 and each electrode element 52.

[0050] In some preferred embodiments, each of the capacitive coupling electrode elements 52 is disk-shaped and has a dielectric layer on one side.

[0051] In some preferred embodiments, each of the capacitive coupling electrode elements 52 comprises a conductive plate having a flat surface, and the dielectric layer is disposed on the flat surface of the conductive plate. In some preferred embodiments, all of the capacitive coupling electrode elements are held in place by a support structure. In some preferred embodiments, the electrical connections to each of the electrode elements 52 consist of traces on a flexible circuit.

[0052] Each of the transducer assemblies 31, 32 also includes a temperature sensor 54 (e.g., a thermistor) positioned at each electrode element 52, thereby enabling each temperature sensor 54 to sense the temperature of each electrode element 52. Each temperature sensor 54 generates a signal representative of the temperature at (e.g., below) each electrode element 52. These signals from the temperature sensors 54 are provided to the analog front end of each controller 85.

[0053] In embodiments in which thermistors are used as temperature sensors 54, temperature readings may be obtained by sending a known current through each thermistor and measuring the voltage that appears across each thermistor. In some embodiments, thermistor-based temperature measurements may be implemented using a bidirectional analog multiplexer to select each thermistor in turn, with a current source generating a known current (e.g., 150 μA) positioned behind the multiplexer so that the known current is sent to whichever thermistor is selected by the analog multiplexer at any given moment. This known current produces a voltage across the selected thermistor, and the temperature of the selected thermistor can be determined by measuring this voltage. Controller 85 executes a program that selects each thermistor in turn and measures the voltage that appears across each thermistor (representing the temperature at the selected thermistor). An example of suitable hardware and procedures that may be utilized to obtain temperature readings from each thermistor is described in U.S. Patent Application Publication No. 2007 / 0129994, which is incorporated herein by reference in its entirety.

[0054] In some preferred embodiments, controller 85 may be implemented using a single-chip microcontroller or PSoC (Programmable System on Chip) with an integrated analog front end and multiplexer. Part numbers suitable for this purpose include CY8C4124LQI-443. In alternative embodiments, other microcontrollers with either an integrated or separate analog front end and multiplexer may be used, as would be apparent to one skilled in the relevant art.

[0055] Although not shown, in alternative embodiments, alternative approaches for coupling to the thermistor (e.g., a traditional voltage divider approach) may be utilized in place of the constant current approach described above. In other alternative embodiments, different types of temperature sensors may be used in place of the thermistor described above. Examples include thermocouples, RTDs, and integrated circuit temperature sensors such as the Analog Devices AD590 and Texas Instruments LM135. Of course, if any of these alternative temperature sensors are used, appropriate modifications to the circuitry (as would be apparent to one skilled in the relevant art) will be required.

[0056] In some embodiments, the controller 85 is programmed to use intelligence built into each transducer assembly 31 to maintain the temperature at all electrode elements below a safety threshold. This can be accomplished, for example, by programming the controller 85 to initiate by setting the digital output of each switch 56 so that it is continuously on (i.e., 100% duty cycle). Then, based on signals arriving via the analog front end of the controller 85, the controller 85 determines whether the temperature at each electrode element exceeds an upper threshold value below the safety threshold. If the controller 85 detects this condition, the controller 85 reduces the duty cycle of the corresponding switch 56 by switching the corresponding digital output at the desired duty cycle. This interrupts current to the corresponding electrode element 52 at the same duty cycle, thereby reducing the average current through the particular electrode element 52 whose temperature has exceeded the upper threshold value. The level of current reduction is determined by the duty cycle. For example, using a 50% duty cycle reduces the current by half, and using a 75% duty cycle reduces the current by 25%.

[0057] In particular, this procedure interrupts current flow to only certain ones of the electrode elements 52 on the transducer assembly 31, but not to the remaining electrode elements 52 on the transducer assembly 31. This eliminates or reduces the need to turn off current flowing through these electrode elements when only a few of these electrode elements are hot.

[0058] A numerical example may be useful to illustrate this point. In the embodiment of FIG. 7 , assume that left and right transducer assemblies 31, 32 are implanted on the left and right sides of a subject's head, all switches 56 in the transducer assemblies 31, 32 are ON with a 100% duty cycle, and the hub / AC voltage generator 30 initially outputs 500 mA of current to the conductors 51. An AC voltage appears between the electrode elements 52 of the left transducer assembly 31 and the right transducer assembly 32, and 500 mA of AC current is capacitively coupled through the electrode elements 52 passing through the subject's head. The controller 85 in each transducer assembly 31, 32 monitors the temperature at each electrode element 52 in that transducer assembly by inputting signals from each temperature sensor 54 through the analog front end of the controller 85. Next, assume that a given one of the electrode elements 52 in the transducer assembly 31 begins to overheat. This condition is reported to the controller 85 in the transducer assembly 31 via a signal from the corresponding temperature sensor 54. When the controller 85 recognizes that a given electrode element 52 is overheating, the controller 85 switches the control signal going to the corresponding switch 56 at a desired duty cycle to periodically interrupt the current to the given electrode element 52 and maintain a lower average current.

[0059] Note that if the duty cycle of only one of the remaining electrode elements 52 is decreasing, it may be possible to maintain the original 500 mA current (and benefit from using all of the current). However, if the duty cycle of a sufficiently large number of electrode elements 52 is decreasing, the original 500 mA current may need to be reduced. To accomplish this, the controller 85 can send a request to the hub / AC voltage generator 30 via a UART within the controller 85. When the hub / AC voltage generator 30 receives this request, the hub / AC voltage generator 30 reduces the output current at the corresponding output OUT1.

[0060] Optionally, the duty cycle selected by the controller 85 may be controlled based on the rate at which a given electrode element 52 heats up (as measured by the temperature sensor 54 and the analog front end of the controller 85) following application of current to the given electrode element 52. More specifically, if the controller 85 determines that a given electrode element 52 is heating up twice as fast as expected, the controller 85 may select a 50% duty cycle for that electrode element. Similarly, if the controller 85 determines that a given electrode element 52 is heating up 10% faster than expected, the controller 85 may select a 90% duty cycle for that electrode element.

[0061] In other embodiments, instead of steadily reducing the average current by lowering the duty cycle, the controller 85 may reduce the average current at a given electrode element 52 based on real-time temperature measurements by switching off the current to the given electrode element 52 and waiting until the temperature, measured using the temperature sensor 54, drops below a second temperature threshold. Once the temperature drops below this second temperature threshold, the controller 85 may restore the current to the given electrode element 52. This may be accomplished, for example, by controlling the state of a control input to a previously switched-off switch 56 so that the switch 56 returns to an ON state, thereby allowing current to flow between the conductors and the respective electrode element 52. In these embodiments, the current to a given electrode element 52 may be repeatedly switched on and off based on real-time temperature measurements to maintain the temperature at the given electrode element 52 below a safety threshold.

[0062] 7, each of the converter assemblies 31, 32 is connected to the hub / AC voltage generator 30 via a respective cable. Notably, only four conductors are required in each cable extending between the converter assembly and the hub / AC voltage generator 30 (i.e., Vcc, data, and ground for implementing serial data communication, and one additional conductor 51 for the AC current TTFields signal).

[0063] 7, it should be noted that each transducer assembly 31, 32 includes nine electrode elements 52, nine switches 56, and nine temperature sensors 54. However, in alternative embodiments, each transducer assembly 31, 32 may include a different number of electrode elements 52 (e.g., between 8 and 25) and a corresponding number of switches and temperature sensors.

[0064] In these embodiments, the decision to adjust the duty cycle or switch off one or more of the switches 56 in a given converter assembly 31, 32 to reduce the average current to one or more of the electrode elements 52 is made locally within each converter assembly 31, 32 by the controller 85 within that converter assembly 31, 32. However, in alternative embodiments, the decision to adjust the duty cycle or switch off one or more of these switches 56 may be made by the hub / AC voltage generator 30 (or another remote device). In these embodiments, the controller 85 within each of the converter assemblies 31, 32 takes temperature readings from each temperature sensor 54 within each converter assembly and transmits those temperature readings to the hub / AC voltage generator 30 via the UART of the controller 85. The hub / AC voltage generator 30 determines which, if any, switches need to have their duty cycle adjusted or which, if any, switches should be switched off based on the received temperature readings and transmits the corresponding instructions to the corresponding controller 85 in the corresponding converter assembly 31, 32. When the controller 85 receives this command from the hub / AC voltage generator 30, the controller 85 responds by setting the digital output to a state that switches off the corresponding switch 56 in a timely manner, thereby implementing the command issued by the hub / AC voltage generator 30. In these embodiments, the hub / AC voltage generator 30 can also be programmed to reduce the output current if a current reduction is necessary to maintain the temperature at each electrode element 52 below a safety threshold.

[0065] In these embodiments, controller 85 may be programmed to operate as a slave to a master controller located in hub / AC voltage generator 30. In these embodiments, controller 85 starts in a quiescent state, where it simply monitors incoming commands from the master controller via UART. Examples of commands that may arrive from the master controller include a "collect temperature data" command, a "send temperature data" command, and a "set switch" command. When controller 85 recognizes that a "collect temperature data" command has arrived, controller 85 takes temperature readings from each of temperature sensors 54 and stores the results in a buffer. When controller 85 recognizes that a "send temperature data" command has arrived, controller 85 performs a procedure to send the previously collected temperature reading from the buffer to hub / AC voltage generator 30 via UART 86. Furthermore, when the controller 85 recognizes that a "set switches" command has arrived, the controller 85 executes a procedure to output the appropriate voltage at the digital output to set each switch 56 to the desired state (i.e., either ON, OFF, or toggling between ON and OFF at the commanded duty cycle) based on the data received from the hub / AC voltage generator 30.

[0066] In the above-described embodiment, a single controller 85 is used in each converter assembly 31, 32 to control the switches 56 in that assembly and to obtain temperature measurements from each temperature sensor 54 in that assembly. In alternative embodiments, instead of using a single controller 85 to control the switches 56 and obtain temperature measurements, these two tasks may be divided between two controllers, with one controller being used only to control the switches 56 and the other controller being used to obtain temperature measurements from each temperature sensor 54 (e.g., using any of the approaches described above). In these embodiments, these two controllers may communicate directly with each other and / or with the hub / AC voltage generator 30.

[0067] In another alternative embodiment (not shown), the temperature measurements do not rely on a local controller positioned near the electrode elements 52. Instead, wires extend from each temperature sensor 54 back to the hub / AC voltage generator 30, and the hub / AC voltage generator uses the signals arriving via these wires to determine the temperature at each temperature sensor 54.

[0068] FIG. 8 is a schematic diagram of a circuit suitable for implementing the switches 56, 56′ in the embodiment of FIG. 7 described above. The circuit includes two field-effect transistors 66, 67 wired in series and configured to allow current to flow in both directions. An example of a suitable FET for this circuit is the BSC320N20NSE (note that the diodes shown in FIG. 8 are inherently contained within the FETs 66, 67 themselves). The series combination of the two FETs 66, 67 either conducts or blocks current depending on the state of a control input received from one of the digital outputs of the controller 85 described above. When the series combination is conducting, current can flow between the shared conductor 51 and each of the electrode elements 52, 52′. On the other hand, when the series combination of FETs 66, 67 is not conducting, current does not flow between the shared conductor 51 and each of the electrode elements 52, 52′.

[0069] Optionally, a current sense circuit 60 may be positioned in series with the switches 56, 56′. The current sense circuit 60 may be implemented using any of a variety of conventional approaches apparent to those skilled in the relevant art. If provided, the current sense circuit 60 generates an output representative of the current, which is reported back to the controller 85 (shown in FIG. 7 ). The controller 85 may then use this information to determine whether the measured current is as expected and take appropriate action if necessary. For example, if an overcurrent condition is detected, the controller 85 may turn off the corresponding switch. Of course, in embodiments in which the current sense circuit 60 is omitted, the current sense circuit 60 should be replaced with a wire (or other conductor) to allow current to flow between the shared conductor 51 and the top leg of the upper FET 66.

[0070] In the illustrated embodiment, the current sense circuit 60 is positioned between the shared conductor 51 and the top leg of the upper FET 66. However, in alternative embodiments, the current sense circuit may be positioned between the bottom leg of the lower FET 67 and each electrode element 52, 52'. In yet another alternative embodiment (not shown), the current sense circuit may be incorporated into the circuitry of the switch itself.

[0071] While the present invention has been disclosed with reference to certain embodiments, numerous modifications, substitutions, and variations to the described embodiments are possible without departing from the sphere and scope of the invention as defined in the appended claims. Accordingly, the present invention is not limited to the described embodiments, but is intended to encompass the full scope defined by the language of the appended claims, and equivalents thereof. [Explanation of symbols]

[0072] 12 port, 14 port, 21 first circuit, 22 second circuit, 23 coil, 24 device, 25 battery, 30 hub / AC voltage generator, 30g AC voltage generator, 30h hub, 31, 32 transducer assembly, 51 wire, 52 electrode element, capacitively coupled electrode element, 52' electrode element, 54 temperature sensor, 56 electronic component, electrically controlled switch, 56' switch, 60 current sensing circuit, 66 upper FET, 67 lower FET, 85 electronic component, controller, OUT1 output, OUT2 output, A, B transducer array, E electrode, electronic block, electronic equipment

Claims

1. 1. A device for delivering a tumor treating electric field, comprising: a plurality of electrode element sets configured to provide a tumor-treating electric field in a treatment area of ​​a human body, each of the electrode element sets configured to be implanted within the human body; a plurality of temperature sensors configured to be implanted within the human body and positioned relative to the electrode element sets to measure temperatures at each of the electrode element sets; at least one circuit configured to be implanted within the human body, the at least one circuit configured and positioned to reduce the number of wires required to acquire temperature measurements from a plurality of the temperature sensors and transfer the acquired temperature measurements to an output; an AC voltage generator configured to apply an AC voltage across the plurality of electrode element sets and to control the current applied to the plurality of electrode element sets based on signals from the plurality of temperature sensors to prevent overheating of the electrode elements; Hub and Equipped with The device wherein all surfaces intended to contact tissue within the human body are biocompatible.

2. The apparatus of claim 1 , wherein each of the electrode element sets comprises a plurality of capacitively coupled electrode elements.

3. The apparatus of claim 1 , wherein each of the temperature sensors comprises a thermistor.

4. 2. The device of claim 1, wherein the plurality of electrode element sets, the plurality of temperature sensors, the at least one circuit, and the hub are all implanted within the human body, but the AC voltage generator is not implanted within the human body.

5. The device of claim 4 , wherein the hub is implanted within the person's thorax.

6. 5. The device of claim 4, further comprising a plurality of multiplexers configured to be implanted within the human body, each of the multiplexers positioned to reduce the number of conductors required to acquire temperature measurements from a respective subset of temperature sensors of the plurality of temperature sensors and transfer the acquired temperature measurements to the hub, each respective subset corresponding to a respective one of the electrode element sets.

7. 5. The device of claim 4, wherein each of the electrode element sets is connected to the hub via a respective cable, and wherein no more than four conductors are used in each cable extending between each of the electrode element sets and the hub.

8. 6. The apparatus of claim 5, wherein the hub collects temperature measurements from each of the electrode element sets, and wherein only one cable extends between the hub and the AC voltage generator, and wherein no more than four conductors are used in the only cable extending between the hub and the AC voltage generator.

9. 1. A device for delivering a tumor treating electric field, comprising: a plurality of electrode element sets configured to provide a tumor-treating electric field in a treatment area of ​​a human body, each of the electrode element sets configured to be implanted within the human body; a plurality of temperature sensors configured to be implanted within the human body and positioned relative to the electrode element sets to measure temperatures at each of the electrode element sets; an AC voltage generator configured to be implanted within the human body, the AC voltage generator configured to apply an AC voltage across the plurality of electrode element sets and to control a current applied to the plurality of electrode element sets based on signals from the plurality of temperature sensors to prevent overheating of the electrode elements; Hub and Equipped with A device wherein all surfaces intended for contact with tissue within the human body are biocompatible.

10. The apparatus of claim 9 , wherein each of the electrode element sets comprises a plurality of capacitively coupled electrode elements.

11. The apparatus of claim 9 , wherein each of the temperature sensors comprises a thermistor.

12. 10. The device of claim 9, wherein the plurality of electrode element sets, the plurality of temperature sensors, the AC voltage generator, and the hub are all implanted within the human body.

13. The device of claim 12 , wherein the hub is implanted within the person's thorax.

14. 13. The device of claim 12, further comprising a plurality of multiplexers configured to be implanted within the human body, each of the multiplexers positioned to reduce the number of wires required to acquire temperature measurements from a respective subset of temperature sensors of the plurality of temperature sensors and transfer the acquired temperature measurements to the hub, each respective subset corresponding to a respective one of the sets of electrode elements.

15. 13. The device of claim 12, wherein each of the electrode element sets is connected to the hub via a respective cable, and wherein no more than four conductors are used in each cable extending between each of the electrode element sets and the hub.

16. 14. The apparatus of claim 13, wherein the hub collects temperature measurements from each of the electrode element sets, and wherein only one cable extends between the hub and the AC voltage generator, and wherein no more than four conductors are used in the only cable extending between the hub and the AC voltage generator.

17. The apparatus of claim 1 , wherein one or more electrode elements of each electrode element set has a temperature sensor associated with the electrode element.

18. 10. The apparatus of claim 1, further comprising a plurality of switches and a controller, the controller being programmed to: (a) determine when a temperature at a given electrode element exceeds a threshold based on signals from each of the temperature sensors; and (b) reduce a duty cycle at a corresponding one of the switches to reduce an average current at the given electrode element.

19. 10. The apparatus of claim 1, further comprising a plurality of switches and a controller, the controller programmed to: (a) determine how fast a given electrode element heats based on signals from each of the temperature sensors; and (b) select a duty cycle for a corresponding one of the switches based on the determined heating rate.

20. 2. The apparatus of claim 1, further comprising a plurality of switches and a controller, the controller being programmed to: (a) determine when a temperature at a given electrode element exceeds a threshold based on signals from each of the temperature sensors; (b) then switch off current to the given electrode element by sending a first control signal to a corresponding one of the switches; (c) then determine when a temperature at the given electrode element drops below a second temperature threshold; and (d) then restore current to the given electrode element by sending a second control signal to a corresponding one of the switches.

21. The apparatus of claim 9 , wherein one or more electrode elements of each electrode element set has a temperature sensor associated with the electrode element.

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